A number of substituted benzimidazoles recently have been discovered which display unusually good antiviral activity; see for example U.S. Pat. Nos. 4,008,243, 4,118,573 and 4,018,790. Among the most active of such benzimidazole antiviral agents are a group of oximes which are 1-sulfonyl-2-amino (or acylamino)-5(6)-hydroximinomethylbenzimidazole derivatives. These compounds are disclosed by Paget et al. in U.S. Pat. No. 4,118,742. As pointed out in the reference, the oximes are prepared by first reacting the corresponding 1-sulfonyl-2-amino (or acylamino)-5(6)-acylbenzimidazoles with hydroxylamine. As might be expected, such procedure affords a mixture, generally a 50:50 mixture, of the syn oxime and the anti oxime. While both the syn and anti isomers display useful antiviral activity, the anti has been determined to be about eight times more potent than the corresponding syn isomer. It therefore would be desirable to have an efficient process for separating such syn and anti isomers. Paget et al. teaches that the syn and anti isomers of a 6-(.alpha.-acetoxyiminobenzyl)benzimidazole can be separated by selective crystallization from ethanol and chloroform. Paget et al. additionally teaches that 1.0 g. of 1-isopropylsulfonyl-2-amino-6-(.alpha.-hydroxyiminobenzyl)-benzimidazole can be chromatographed over a high pressure chromatography column using a 50:50 methanol-water eluant to provide 70 mg of 1-isopropylsulfonyl-2-amino-6-(anti-.alpha.-hydroxyiminobenzyl)benzimidazo le and 30 mg. of the corresponding syn isomer. These processes suffer in several respects. First, substantial product loss is encountered. Secondly, neither process affords an isomer in greater than about eighty percent purity. Moreover, chromatographic separation is time consuming and does not lend itself to large scale production.
An object of this invention is to provide a process for separating syn and anti oximes so that the respective isomers can be obtained in greater than about ninety-five percent purity. Another object is to provide a process whereby commercial quantities of anti oximes can be separated from the corresponding syn oximes.